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Mdma Clinical Trials


The effects of THC on Resting State fMRI.


To see complete record on www.trialregister.nl, please visit this link

Id: NTR1533

Organisation Name: CHDR in cooperation with LUMC

Overal Status: Planned

Start Date: 2009-01-01

Lead Sponsor: CHDR in cooperation with LUMC

Brief Summary: Title:

A randomized, double blind, placebo-controlled, 2-way cross-over study to investigate the effects of inhaled THC on resting state functional magnetic resonance imaging in healthy volunteers.



Investigator/trial location:

CHDR, Leiden, The Netherlands
LUMC, Leiden, The Netherlands.



Rationale:

Cannabinoid receptor (CB) ligands could have beneficial effects on several disorders associated with impairments of certain regions of the central nervous system (CNS), such as obesity, substance abuse and pain.

To gain understanding of the pharmacological activity of CNS drugs, pharmacodynamic (PD) effects are assessed using a variety of validated PD measures. Functional Magnetic Resonance Imaging (fMRI) measures blood oxygen level dependent (BOLD) signals that are associated with neuronal activity, and can thus give information on brain activation patterns of a CNS-active drug. Ideally, drug-induced fMRI-changes would be independent of tasks, and merely related to the concentrations and pharmacological effects of the drugs on different brain areas. Until recently, this was not technically possible, but innovations in signal analysis now allow the accurate detection of resting-state fMRI-signals, activated by a pharmacological compound instead of by a task. The main objective of the current study is to detect resting-state fMRI-effects induced by CB-agonist Ä9-tetrahydrocannabidiol (THC).




Study objectives:

Primary Objective:

To investigate the effects of THC on fMRI activation patterns in healthy volunteers.



Secondary objectives:

1. To assess the feasibility of pharmacokinetic/pharmacodynamic (PK/PD)-analyses for THC-induced fMRI-activation patterns;

2. To assess the pharmacokinetics of THC;

3. Other pharmacodynamic effects (visual analogue scales).




Study design:

1. Randomized, double blind, placebo-controlled, 2-way cross-over design;

2. Treatment arms;

3. THC (2, 6, 6 mg);

4. Placebo THC;

Wash-out period: 2 weeks.




Study population:

Total expected number of subjects:

12 (6 male, 6 female).




Main selection criteria:

Healthy right-handed occasional cannabis users (<1/week).



Investigational products:

Dosing rationale:

THC doses that will be used have shown to be effective in inducing effects on CNS and heart rate in previous studies performed at CHDR.

Formulations:

1. THC 2, 4 and 6 mg in ethanol 200, 600 and 600 µL, in 8 l of air;

2. THC Placebo: ethanol 200, 600 and 600 µL, in 8 l of air.



Routes of administration:

Intrapulmonary.



Dose regimen/duration:

Single repeated doses of THC 2, 6, 6 mg with 1.5 hour intervals.




Endpoints:

1. Pharmacodynamics:

2. Resting state network (RSN) activity;

3. Arterial spin labeling (ASL): whole brain, voxel-wise cerebral blood flow (CBF) (milliliters of blood per 100g of tissue per minute) and CBF changes due to drug administration;

4. Visual Analogue Scale (VAS) mood & alertness (Bond and Lader);

5. VAS feeling high, internal & external perception (Bowdle);

6. Heart rate;

7. Prolactin, LH, FSH, cortisol levels;

8. Pharmacokinetics:

THC and its metabolites 11-hydroxy-THC and 11-nor-9-carboxy-THC.




Assessment schedule:

On study days, subjects will inhale THC or placebo at three time points with 1.5 h intervals. The dosages of THC are 2, 6, and 6 mg. One scanning sessions is planned before dosing, and two scanning sessions after each inhalation. After the last inhalation, two extra scanning sessions are scheduled.




Duration of study period (per subject):

In total per subject: approximately 28 days (4 weeks or 1 month).

14 days for screening.

14 days for wash out period.

2 study periods (1 day).

Country: Netherlands



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